genome-wide association for the rest of us: introduction and goals national human genome research...
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Genome-Wide Association for the Rest of Us:
Introduction and GoalsNational Human Genome Research
Institute
National Institutes of
Health
U.S. Department of Health and
Human Services
U.S. Department of Health and Human Services
National Institutes of Health
National Human Genome Research Institute
Teri A. Manolio, M.D., Ph.D.Senior Advisor to the Director, NHGRI,
for Population GenomicsDirector, Office of Population Genomics
June 22, 2007
Hokusai, K. The Great Wave
2007: The Year of GWA Studies?
Hokusai, K. The Great Wave
2007: The Year of GWA Studies?
Hokusai, K. The Great Wave 27May2007
2007: The Year of GWA Studies?
Sciencexpress, 3May2007
2007: The Year of GWA Studies?
Sciencexpress, 26Apr2007
2007: The Year of GWA Studies?
Nature Genetics, 1Apr2007
2007: The Year of GWA Studies?
26Oct2006
19Oct2006
10Mar2005
Sciencexpress
2007: The Year of GWA Studies?
What is a GWA Study?
• Method for interrogating all 10 million variable points across human genome
• Variation inherited in groups, or blocks, so not all 10 million points have to be tested
• Blocks are shorter (so need to test more points) the less closely people are related
• Technology now allows studies in unrelated persons, assuming ~10,000 base pair lengths in common (300,000 - 500,000 markers)
http://www.broad.mit.edu/diabetes/scandinavs/type2.html
Genome-Wide Scan for Type 2 Diabetes in a Scandinavian Cohort
Background and Opportunities
• Understanding of genome structure provides unprecedented opportunities to define genetic contributions to health and disease, particularly in relation to environmental effects
• Progress in application of genomic knowledge to health somewhat hampered by differences between disciplines:
– Genetics/genomics
– Population-based epidemiology
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Bayes Factors
HapMap
gene deserts
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ntsdbG
aP
Bayes Factors
CEL files
inversion
HapMap
gene deserts
calling
algorithm
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ancestral markers
anonymized
gene deserts
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dbGaP
population
population
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Q-Q plots
whole genom
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amplificationBayes Factors
calling
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P3G
Hardy-Weinberg deviation
HuGENet
IMPUTATIONclustering
algorithms
minor allele frequency
CEL files
inversion
linkage disequilibrium
HapMap gene-environme
nt interaction
admixture
admixture
Larson, G. The Complete Far Side. 2003.
Structure of Session• Bridging epidemiology and genomics (W. Post and
D. Nickerson)
• Design of initial and replication studies (D. Hunter)• Genotyping platforms and quality control (E. Pugh)
• Selection of markers to carry forward (N. Cox)• Managing and analyzing data (L. Scott)
• Promoting collaborations (R. Hoover)• Data deposition and access (J. Ostell)
• Community concerns (D. Levy)• Data sharing and collaborations (A. Singleton)
• Synthesizing findings (M. Gwinn)• Best practices, additional research (Panel)
A Word from Our Sponsor…
http://genesandenvironment.nih.gov/
Genes, Environment and Health Initiative (GEI)
• NIH-wide initiative of the Secretary, HHS• Aims to accelerate understanding of genetic
and environmental contributions to health and disease
• Two components:– Genetic analyses of case-control studies of
common disease ($26M per year for four years)
– Development of innovative technologies to measure environmental exposures, diet, and physical activity ($14M per year for four years)
NHGRI Office of Population Genomics
http://www.genome.gov/19518660
NHGRI Office of Population Genomics
• Established to facilitate application of genomic knowledge to health, by promoting multi-disciplinary research and applying genomic technologies to population studies
• Key goal: Support cross-disciplinary training for geneticists and epidemiologists– Multi-IC Symposia on Application of Genomic
Technologies to Population Studies– GWA Studies for the Rest of Us– Designing Geneticists (ASHG, October 2007)
http://www.genome.gov/19518660
Many Thanks to SER…
Especially Mike Bracken and Peggy Christensen!
Housekeeping Items
• Videotaping for webarchive at http://genesandenvironment.nih.gov/, please use microphones during discussion sessions
• Two 20-minute breaks and 45-minute lunch
• Unable to give you lunch, local lunch list provided
• Homework: Closing discussion on best practices and research/tools needed will be of great value to NHGRI and GEI, perhaps SER
• Speakers selected for their laid-back genes, ask if you need to know something to go further
• There are no stupid questions!
Larson, G. The Complete Far Side. 2003.
Watch for PowerPoints and Video
http://genesandenvironment.nih.gov/
Larson, G. The Complete Far Side. 2003.
